The goal of this proposal is to develop and validate a device for measuring the chemical and molecular composition of coronary atherosclerotic plaques in living human patients. The ability to measure chemicals and molecules in human coronary arteries could improve our understanding of plaque formation, plaque progression, the events leading to coronary thrombosis, and the response to pharmacologic therapy. Intracoronary Raman spectroscopy is a promising technology for obtaining this information. With Raman spectroscopy, a laser illuminates a tissue sample and a small portion of the light imparts some of its energy to the tissue's chemical bonds. Since the amount of energy lost is specific to each individual chemical bond, the spectrum of the Raman scattered light can be used to determine the tissue's chemical and molecular composition. We have recently developed a prototype catheter and have demonstrated that Raman spectra can be obtained from a single spot within the coronary arteries of living swine. In this proposal, we will develop a next-generation Raman system and catheter that fulfills the requirements for human use and that is capable of obtaining high-quality Raman spectral maps along the circumference of a coronary artery, and possibly even over entire coronary segments. While Raman spectroscopy has already been shown to be capable of measuring many plaque chemicals and molecules, we will additionally investigate its potential to measure other molecules that are currently thought to precipitate acute coronary syndromes, including those associated with necrotic core lesions, the extracellular matrix, and oxidative stress. Finally, we will conduct a clinical study in 60 patients to demonstrate the safety and feasibility of intracoronary Raman spectroscopy. This study will provide insight on the clinical utility of this new method by comparing chemical and molecular information obtained from patients with different presentations of coronary artery disease.